The induction of immunological tolerance in T cells can possibly occur prior to their entry into the thymus, during thymic differentiation or after the cells have emigrated from the thymus. Experimental systems have been constructed to investigate the susceptibility of T cells or their precursors to tolerance induction during the various phases of their differentiation. The basic model consists of murine thymus engrafted radiation bone marrow chimeras in which the cell surface alloantigens can, in theory be specifically localized in the extra-thymic or intra-thymic differentiation environments. The results demonstrate that tolerance to MHC encoded antigens can occur pre-thymically and intra-thymically and that tolerance to M1s encoded antigens can occur both intra-thymically and post-thymically but not pre-thymically. In addition, it has been shown that in chimeric mice in which the engrafted thymus is the only MHC allogeneic element, thymically induced tolerance to MHC encoded alloantigens is not sufficient to prevent autoreactivity since peripheral T cells were reactive to the thymic MHC encoded antigens. In sum, these results demonstrate that tolerance to various cell surface antigens occurs at different stages of T cell development and that the thymus is not a unique site of tolerance induction for maturing T cells.